The Duke Medical Scientist Training Program (MSTP) is one of three original MSTPs funded by NIGMS in 1966, and it has been continuously funded since that time. This competing continuation application requests funding for 32 trainees, an increase of one position over the current level of support. The goal of the Duke MSTP is to prepare young physician-scientists for careers in biomedical research and academic medicine by providing comprehensive training in both scientific research and clinical medicine through completion of both the MD and PhD degrees. The program's mission is to provide an intellectual foundation that will allow trainees from diverse backgrounds to become the future thought leaders in biomedical science and academic medicine in the US. To accomplish these goals, the Program is built on a unique medical school curriculum that integrates medical education with original scholarly investigation. The defining feature of the Duke curriculum is that all medical students engage in significant scholarly activity in the third year. As a consequence, the core medical education takes place over three years, rather than four, with the preclinical basic sciences condensed into the first year and core clinical clerkships taught in the second year. This curriculum is therefore ideally suited to MSTP trainees, as it provides comprehensive clinical training prior to PhD training, allowing students to align their research interests with teir long-term clinical interests as well as shortening the time to the dual degree. Over the past 5 years, the Duke MSTP has undergone a number of major changes and improvements after it came under new directorship in 2006: 1) The admissions process was revamped to ensure recruitment of top tier applicants while also addressing the problem of unacceptably high attrition rates; 2) Program administration has been modified to ensure adequate oversight of the director and to provide enhanced input from a broader range of outstanding faculty; 3) Improved trainee oversight has been incorporated at multiple stages of the program; 4) Numerous program activities have been added to ensure adequate program-wide training opportunities and to foster program unity; 5) An accelerated rotation structure has been added to allow time for trainees to take Step 1 of the USMLE and to transition to their thesis labs by the middle of first-year of graduate school; 6) Activities to ensure that clinical skills are not lost during thePhD years have been added; 7) Institutional support has improved dramatically; and 8) Multiple opportunities for trainees to influence their own career development have been incorporated. These new program initiatives have built on the Duke MSTP's tradition of excellent MD-PhD training to substantially improve and revitalize the program, preparing it for growth over the next 5 years to a new steady state of approximately 88 students.